Conformational requirements of alpha 2-adrenergic receptors

Mol Pharmacol. 1982 Mar;21(2):259-61.

Abstract

The conformationally restrained trans-extended and cis-folded isomers of 2-(3,4-dihydroxyphenyl)cyclobutylamine were used to establish the conformational requirements of presynaptic alpha 2-adrenergic receptors in the field-stimulated guinea pig ileum. The trans-extended isomer produced a concentration-dependent inhibition of the twitch response with an EC50 of 34 microM. The cis-folded analogue failed to produce a significant inhibition of the twitch response at concentrations up to 1 mM. These results suggest that the presynaptic alpha 2-adrenergic receptor prefers phenethylamines in the trans-extended conformation over the cis-folded conformation. The conformational requirements of alpha 1- and alpha 2-adrenergic receptors appear to be similar.

MeSH terms

  • Animals
  • Dopamine / pharmacology
  • Electric Stimulation
  • Guinea Pigs
  • In Vitro Techniques
  • Molecular Conformation
  • Muscle Contraction
  • Muscle, Smooth / drug effects
  • Norepinephrine / analogs & derivatives
  • Norepinephrine / pharmacology
  • Receptors, Adrenergic / metabolism*
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism*
  • Stereoisomerism
  • Sulpiride / pharmacology

Substances

  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha
  • Sulpiride
  • Dopamine
  • Norepinephrine